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1. Mobilization of an ICEclc-Like Element as a Potential Mechanism for the Spread of IMP-13 Carbapenemase in Pseudomonas aeruginosa

Author: Léa Bientz, Ulysse Guyet, Jennifer Guiraud, Mathieu Metifiot, Mikeldi Moulieras, Sabine Aillerie, Laure Coulange-Mayonnove, Bachir Boureima-Abdou, Alexis Groppi, Macha Nikolski, Cécile Bébéar, Sabine Pereyre, and Véronique Dubois
Subjects: Pseudomonas aeruginosa, IMP-13 carbapenemase, ICEclc-like element, Horizontal gene transfer, Antibiotic resistance, Microbiology, QR1-502
Abstract: Carbapenem-resistant Pseudomonas aeruginosa is a global public health concern. IMP-13 is a carbapenemase that was described for the first time in 2001 but is often underestimated due to poor hydrolysis of carbapenems and a lack of molecular detection. The aim of this study was to characterize the genetic support of blaIMP-13 in P. aeruginosa and to assess the ability of mobile genetic elements to disseminate this resistance. A retrospective analysis conducted between 2010 and 2020 revealed eight multiresistant P. aeruginosa isolates by their production of the carbapenemase IMP-13 in Bordeaux. Additionally, three of the studied isolates exhibited high-level resistance to imipenem and imipenem-relebactam that was linked to an insertion sequence in the oprD gene. Successful mating was achieved, and transconjugants and parental clinical isolate genomes were sequenced. All clinical isolates were found to be ST621 strains. The data revealed that blaIMP-13 was carried on an Integrative and Conjugative Element (ICEclc-like) of 88,589 bp with a 62% GC content harboring 85 CDSs, and was inserted at the tRNAGly locus PA0729.1. The ICE was identical in the eight studied clinical isolates and in all the ST621 strains found in the databases. The conjugation rate was low, at approximately 10–8 transconjugants per donor and ICE transfer appeared to mobilize some adjacent parental genes located immediately downstream of the ICE. In conclusion, these results suggest that even if the spread of blaIMP-13 is mainly due to an epidemic ST621 clone, the mobilization of a blaIMP-13-carrying ICEclc-like element is possible and should not be underestimated.
Published: 2025
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2. Holistic understanding of trimethoprim resistance in Streptococcus pneumoniae using an integrative approach of genome-wide association study, resistance reconstruction, and machine learning

Author: Nguyen-Phuong Pham, Hélène Gingras, Chantal Godin, Jie Feng, Alexis Groppi, Macha Nikolski, Philippe Leprohon, and Marc Ouellette
Subjects: Streptococcus pneumoniae, trimethoprim, drug resistance mechanisms, genome-wide association study, machine learning, Microbiology, QR1-502
Abstract: ABSTRACT Antimicrobial resistance (AMR) is a public health threat worldwide. Next-generation sequencing (NGS) has opened unprecedented opportunities to accelerate AMR mechanism discovery and diagnostics. Here, we present an integrative approach to investigate trimethoprim (TMP) resistance in the key pathogen Streptococcus pneumoniae. We explored a collection of 662 S. pneumoniae genomes by conducting a genome-wide association study (GWAS), followed by functional validation using resistance reconstruction experiments, combined with machine learning (ML) approaches to predict TMP minimum inhibitory concentration (MIC). Our study showed that multiple additive mutations in the folA and sulA loci are responsible for TMP non-susceptibility in S. pneumoniae and can be used as key features to build ML models for digital MIC prediction, reaching an average accuracy within ±1 twofold dilution factor of 86.3%. Our roadmap of in silico analysis—wet-lab validation—diagnostic tool building could be adapted to explore AMR in other combinations of bacteria–antibiotic.IMPORTANCEIn the age of next-generation sequencing (NGS), while data-driven methods such as genome-wide association study (GWAS) and machine learning (ML) excel at finding patterns, functional validation can be challenging due to the high numbers of candidate variants. We designed an integrative approach combining a GWAS on S. pneumoniae clinical isolates, followed by whole-genome transformation coupled with NGS to functionally characterize a large set of GWAS candidates. Our study validated several phenotypic folA mutations beyond the standard Ile100Leu mutation, and showed that the overexpression of the sulA locus produces trimethoprim (TMP) resistance in Streptococcus pneumoniae. These validated loci, when used to build ML models, were found to be the best inputs for predicting TMP minimal inhibitory concentrations. Integrative approaches can bridge the genotype-phenotype gap by biological insights that can be incorporated in ML models for accurate prediction of drug susceptibility.
Published: 2024
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3. Population genomics of apricots unravels domestication history and adaptive events

Author: Alexis Groppi, Shuo Liu, Amandine Cornille, Stéphane Decroocq, Quynh Trang Bui, David Tricon, Corinne Cruaud, Sandrine Arribat, Caroline Belser, William Marande, Jérôme Salse, Cécile Huneau, Nathalie Rodde, Wassim Rhalloussi, Stéphane Cauet, Benjamin Istace, Erwan Denis, Sébastien Carrère, Jean-Marc Audergon, Guillaume Roch, Patrick Lambert, Tetyana Zhebentyayeva, Wei-Sheng Liu, Olivier Bouchez, Céline Lopez-Roques, Rémy-Félix Serre, Robert Debuchy, Joseph Tran, Patrick Wincker, Xilong Chen, Pierre Pétriacq, Aurélien Barre, Macha Nikolski, Jean-Marc Aury, Albert Glenn Abbott, Tatiana Giraud, and Véronique Decroocq
Subjects: Science
Abstract: The evolutionary and domestication history of apricots is poorly understood. Here, the authors provide four apricot high-quality genome assemblies, the genomes of 578 accessions from natural and cultivated populations, and show that Chinese and European apricots constitute two different gene pools, resulting from independent domestication events.
Published: 2021
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4. Novel analytical methods to interpret large sequencing data from small sample sizes

Author: Florence Lichou, Sébastien Orazio, Stéphanie Dulucq, Gabriel Etienne, Michel Longy, Christophe Hubert, Alexis Groppi, Alain Monnereau, François-Xavier Mahon, and Béatrice Turcq
Subjects: Chronic myeloid leukemia, Next-generation sequencing, Pharmacogenetics, Small sample size, Statistics, Factorial correspondence analysis, Medicine, Genetics, QH426-470
Abstract: Abstract Background Targeted therapies have greatly improved cancer patient prognosis. For instance, chronic myeloid leukemia is now well treated with imatinib, a tyrosine kinase inhibitor. Around 80% of the patients reach complete remission. However, despite its great efficiency, some patients are resistant to the drug. This heterogeneity in the response might be associated with pharmacokinetic parameters, varying between individuals because of genetic variants. To assess this issue, next-generation sequencing of large panels of genes can be performed from patient samples. However, the common problem in pharmacogenetic studies is the availability of samples, often limited. In the end, large sequencing data are obtained from small sample sizes; therefore, classical statistical analyses cannot be applied to identify interesting targets. To overcome this concern, here, we described original and underused statistical methods to analyze large sequencing data from a restricted number of samples. Results To evaluate the relevance of our method, 48 genes involved in pharmacokinetics were sequenced by next-generation sequencing from 24 chronic myeloid leukemia patients, either sensitive or resistant to imatinib treatment. Using a graphical representation, from 708 identified polymorphisms, a reduced list of 115 candidates was obtained. Then, by analyzing each gene and the distribution of variant alleles, several candidates were highlighted such as UGT1A9, PTPN22, and ERCC5. These genes were already associated with the transport, the metabolism, and even the sensitivity to imatinib in previous studies. Conclusions These relevant tests are great alternatives to inferential statistics not applicable to next-generation sequencing experiments performed on small sample sizes. These approaches permit to reduce the number of targets and find good candidates for further treatment sensitivity studies.
Published: 2019
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5. Targeting CAMKK2 and SOC Channels as a Novel Therapeutic Approach for Sensitizing Acute Promyelocytic Leukemia Cells to All-Trans Retinoic Acid

Author: Faten Merhi, Karla Alvarez-Valadez, Jenifer Trepiana, Claire Lescoat, Alexis Groppi, Jean-William Dupuy, Pierre Soubeyran, Guido Kroemer, Pierre Vacher, and Mojgan Djavaheri-Mergny
Subjects: differentiation, cell death, autophagy, cancer, ORAI1, STIM1, Cytology, QH573-671
Abstract: Calcium ions (Ca2+) play important and diverse roles in the regulation of autophagy, cell death and differentiation. Here, we investigated the impact of Ca2+ in regulating acute promyelocytic leukemia (APL) cell fate in response to the anti-cancer agent all-trans retinoic acid (ATRA). We observed that ATRA promotes calcium entry through store-operated calcium (SOC) channels into acute promyelocytic leukemia (APL) cells. This response is associated with changes in the expression profiles of ORAI1 and STIM1, two proteins involved in SOC channels activation, as well as with a significant upregulation of several key proteins associated to calcium signaling. Moreover, ATRA treatment of APL cells led to a significant activation of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and its downstream effector AMP-activated protein kinase (AMPK), linking Ca2+ signaling to autophagy. Pharmacological inhibition of SOC channels and CAMKK2 enhanced ATRA-induced cell differentiation and death. Altogether, our results unravel an ATRA-elicited signaling pathway that involves SOC channels/CAMKK2 activation, induction of autophagy, inhibition of cellular differentiation and suppression of cell death. We suggest that SOC channels and CAMKK2 may constitute novel drug targets for potentiating the anti-cancer effect of ATRA in APL patients.
Published: 2021
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6. Pacific Biosciences Sequencing and IMGT/HighV-QUEST Analysis of Full-Length Single Chain Fragment Variable from an In Vivo Selected Phage-Display Combinatorial Library

Author: Audrey Hemadou, Véronique Giudicelli, Melissa Laird Smith, Marie-Paule Lefranc, Patrice Duroux, Sofia Kossida, Cheryl Heiner, N. Lance Hepler, John Kuijpers, Alexis Groppi, Jonas Korlach, Philippe Mondon, Florence Ottones, Marie-Josée Jacobin-Valat, Jeanny Laroche-Traineau, and Gisèle Clofent-Sanchez
Subjects: human antibody, IMGT/HighV-QUEST, immunoinformatics, immunoglobulin, Pacific Biosciences sequencing, phage combinatorial library, Immunologic diseases. Allergy, RC581-607
Abstract: Phage-display selection of immunoglobulin (IG) or antibody single chain Fragment variable (scFv) from combinatorial libraries is widely used for identifying new antibodies for novel targets. Next-generation sequencing (NGS) has recently emerged as a new method for the high throughput characterization of IG and T cell receptor (TR) immune repertoires both in vivo and in vitro. However, challenges remain for the NGS sequencing of scFv from combinatorial libraries owing to the scFv length (>800 bp) and the presence of two variable domains [variable heavy (VH) and variable light (VL) for IG] associated by a peptide linker in a single chain. Here, we show that single-molecule real-time (SMRT) sequencing with the Pacific Biosciences RS II platform allows for the generation of full-length scFv reads obtained from an in vivo selection of scFv-phages in an animal model of atherosclerosis. We first amplified the DNA of the phagemid inserts from scFv-phages eluted from an aortic section at the third round of the in vivo selection. From this amplified DNA, 450,558 reads were obtained from 15 SMRT cells. Highly accurate circular consensus sequences from these reads were generated, filtered by quality and then analyzed by IMGT/HighV-QUEST with the functionality for scFv. Full-length scFv were identified and characterized in 348,659 reads. Full-length scFv sequencing is an absolute requirement for analyzing the associated VH and VL domains enriched during the in vivo panning rounds. In order to further validate the ability of SMRT sequencing to provide high quality, full-length scFv sequences, we tracked the reads of an scFv-phage clone P3 previously identified by biological assays and Sanger sequencing. Sixty P3 reads showed 100% identity with the full-length scFv of 767 bp, 53 of them covering the whole insert of 977 bp, which encompassed the primer sequences. The remaining seven reads were identical over a shortened length of 939 bp that excludes the vicinity of primers at both ends. Interestingly these reads were obtained from each of the 15 SMRT cells. Thus, the SMRT sequencing method and the IMGT/HighV-QUEST functionality for scFv provides a straightforward protocol for characterization of full-length scFv from combinatorial phage libraries.
Published: 2017
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7. Early Medieval Muslim Graves in France: First Archaeological, Anthropological and Palaeogenomic Evidence.

Author: Yves Gleize, Fanny Mendisco, Marie-Hélène Pemonge, Christophe Hubert, Alexis Groppi, Bertrand Houix, Marie-France Deguilloux, and Jean-Yves Breuil
Subjects: Medicine, Science
Abstract: The rapid Arab-Islamic conquest during the early Middle Ages led to major political and cultural changes in the Mediterranean world. Although the early medieval Muslim presence in the Iberian Peninsula is now well documented, based in the evaluation of archeological and historical sources, the Muslim expansion in the area north of the Pyrenees has only been documented so far through textual sources or rare archaeological data. Our study provides the first archaeo-anthropological testimony of the Muslim establishment in South of France through the multidisciplinary analysis of three graves excavated at Nimes. First, we argue in favor of burials that followed Islamic rites and then note the presence of a community practicing Muslim traditions in Nimes. Second, the radiometric dates obtained from all three human skeletons (between the 7th and the 9th centuries AD) echo historical sources documenting an early Muslim presence in southern Gaul (i.e., the first half of 8th century AD). Finally, palaeogenomic analyses conducted on the human remains provide arguments in favor of a North African ancestry of the three individuals, at least considering the paternal lineages. Given all of these data, we propose that the skeletons from the Nimes burials belonged to Berbers integrated into the Umayyad army during the Arab expansion in North Africa. Our discovery not only discusses the first anthropological and genetic data concerning the Muslim occupation of the Visigothic territory of Septimania but also highlights the complexity of the relationship between the two communities during this period.
Published: 2016
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8. Composting-Like Conditions Are More Efficient for Enrichment and Diversity of Organisms Containing Cellulase-Encoding Genes than Submerged Cultures.

Author: Senta Heiss-Blanquet, Françoise Fayolle-Guichard, Vincent Lombard, Agnès Hébert, Pedro M Coutinho, Alexis Groppi, Aurélien Barre, and Bernard Henrissat
Subjects: Medicine, Science
Abstract: Cost-effective biofuel production from lignocellulosic biomass depends on efficient degradation of the plant cell wall. One of the major obstacles for the development of a cost-efficient process is the lack of resistance of currently used fungal enzymes to harsh conditions such as high temperature. Adapted, thermophilic microbial communities provide a huge reservoir of potentially interesting lignocellulose-degrading enzymes for improvement of the cellulose hydrolysis step. In order to identify such enzymes, a leaf and wood chip compost was enriched on a mixture of thermo-chemically pretreated wheat straw, poplar and Miscanthus under thermophile conditions, but in two different set-ups. Unexpectedly, metagenome sequencing revealed that incubation of the lignocellulosic substrate with compost as inoculum in a suspension culture resulted in an impoverishment of putative cellulase- and hemicellulase-encoding genes. However, mimicking composting conditions without liquid phase yielded a high number and diversity of glycoside hydrolase genes and an enrichment of genes encoding cellulose binding domains. These identified genes were most closely related to species from Actinobacteria, which seem to constitute important players of lignocellulose degradation under the applied conditions. The study highlights that subtle changes in an enrichment set-up can have an important impact on composition and functions of the microcosm. Composting-like conditions were found to be the most successful method for enrichment in species with high biomass degrading capacity.
Published: 2016
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9. Synthesis of Flavonol-Bearing Probes for Chemoproteomic and Bioinformatic Analyses of Asteraceae Petals in Search of Novel Flavonoid Enzymes

Author: Quideau, Karl Kempf, Oxana Kempf, Yoan Capello, Christian Molitor, Claire Lescoat, Rana Melhem, Stéphane Chaignepain, Elisabeth Génot, Alexis Groppi, Macha Nikolski, Heidi Halbwirth, Denis Deffieux, and Stéphane
Subjects: plant polyphenols, Asteraceae UV-honey guides, higher hydroxylated flavonols, flavonoid biosynthesis, chemoproteomics, bioinformatics
Abstract: This study aimed at searching for the enzymes that are responsible for the higher hydroxylation of flavonols serving as UV-honey guides for pollinating insects on the petals of Asteraceae flowers. To achieve this aim, an affinity-based chemical proteomic approach was developed by relying on the use of quercetin-bearing biotinylated probes, which were thus designed and synthesized to selectively and covalently capture relevant flavonoid enzymes. Proteomic and bioinformatic analyses of proteins captured from petal microsomes of two Asteraceae species (Rudbeckia hirta and Tagetes erecta) revealed the presence of two flavonol 6-hydroxylases and several additional not fully characterized proteins as candidates for the identification of novel flavonol 8-hydroxylases, as well as relevant flavonol methyl- and glycosyltransferases. Generally speaking, this substrate-based proteome profiling methodology constitutes a powerful tool for the search for unknown (flavonoid) enzymes in plant protein extracts.
Published: 2023
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10. Targeting CAMKK2 and SOC Channels as a Novel Therapeutic Approach for Sensitizing Acute Promyelocytic Leukemia Cells to All-Trans Retinoic Acid

Author: Jean-William Dupuy, Karla Alvarez-Valadez, Alexis Groppi, Claire Lescoat, Jenifer Trepiana, Guido Kroemer, Pierre Vacher, Faten Merhi, Pierre Soubeyran, Mojgan Djavaheri-Mergny, Institut Bergonié [Bordeaux], UNICANCER, Laboratory of Stem Cells [Lebanese, Beirut] (ER045-PRASE), Lebanese University [Beirut] (LU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut Gustave Roussy (IGR), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Plateforme Protéome [Bordeaux], Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2]-Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), and Groppi, Alexis
Subjects: Acute promyelocytic leukemia, AMPK, Programmed cell death, autophagy, QH301-705.5, STIM1, Cellular differentiation, Calcium-Calmodulin-Dependent Protein Kinase Kinase, Tretinoin, Article, 03 medical and health sciences, 0302 clinical medicine, Leukemia, Promyelocytic, Acute, Cell Line, Tumor, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, cancer, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Biology (General), Protein kinase A, neoplasms, 030304 developmental biology, Calcium signaling, CAMKK2, SOC channels, 0303 health sciences, therapy, Chemistry, Adenylate Kinase, Cell Differentiation, General Medicine, differentiation, medicine.disease, 3. Good health, Cell biology, Up-Regulation, Enzyme Activation, ORAI1, cell death, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, resistance to therapy, Calcium, Calcium Channels, Signal transduction, Granulocytes
Abstract: Calcium ions (Ca2+) play important and diverse roles in the regulation of autophagy, cell death and differentiation. Here, we investigated the impact of Ca2+ in regulating acute promyelocytic leukemia (APL) cell fate in response to the anti-cancer agent all-trans retinoic acid (ATRA). We observed that ATRA promotes calcium entry through store-operated calcium (SOC) channels into acute promyelocytic leukemia (APL) cells. This response is associated with changes in the expression profiles of ORAI1 and STIM1, two proteins involved in SOC channels activation, as well as with a significant upregulation of several key proteins associated to calcium signaling. Moreover, ATRA treatment of APL cells led to a significant activation of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) and its downstream effector AMP-activated protein kinase (AMPK), linking Ca2+ signaling to autophagy. Pharmacological inhibition of SOC channels and CAMKK2 enhanced ATRA-induced cell differentiation and death. Altogether, our results unravel an ATRA-elicited signaling pathway that involves SOC channels/CAMKK2 activation, induction of autophagy, inhibition of cellular differentiation and suppression of cell death. We suggest that SOC channels and CAMKK2 may constitute novel drug targets for potentiating the anti-cancer effect of ATRA in APL patients F.M. was supported by a postdoctoral fellowship from the “Aquitaine Regional Council” (to MDM). K.A.-V. is supported by the Mexican National Council of Science and Technology (CONACYT, funding #757821). This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale (INSERM), a grant from SIRIC BRIO (to M.D.M.), Federation de recherche Transbiomed (to M.D-M.) and contributes to the IdEx Université de Paris ANR-18-IDEX-0001. GK is supported by the Ligue contre le Cancer (équipe labellisée); Agence National de la Recherche (ANR)—Projets blancs; AMMICa US23/CNRS UMS3655; Association pour la recherche sur le cancer (ARC); Association “Ruban Rose”; Cancéropôle Ile-de-France; Fondation pour la Recherche Médicale (FRM); a donation by Elior; Equipex Onco-Pheno-Screen; European Joint Programme on Rare Diseases (EJPRD); Gustave Roussy Odyssea, the European Union Horizon 2020 Projects Oncobiome and Crimson; Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LabEx Immuno-Oncology (ANR-18-IDEX-0001); the Leducq Foundation; a Cancer Research ASPIRE Award from the Mark Foundation; the RHU Torino Lumière; Seerave Foundation; SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); and SIRIC Cancer Research and Personalized Medicine (CARPEM). This study contributes to the IdEx Université de Paris ANR-18-IDEX-0001.
Published: 2021
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11. Population genomics of apricots unravels domestication history and adaptive events

Author: Patrick Wincker, Corinne Cruaud, William Marande, Guillaume Roch, Amandine Cornille, Nathalie Rodde, Jean-Marc Aury, Robert Debuchy, Quynh Trang Bui, David Tricon, Pierre Pétriacq, Jérôme Salse, Rémy Félix Serre, Sandrine Arribat, Tatiana Giraud, Alexis Groppi, Erwan Denis, Wassim Rhalloussi, Céline Lopez-Roques, Véronique Decroocq, Olivier Bouchez, Shuo Liu, Macha Nikolski, Jean Marc Audergon, Sébastien Carrère, Xilong Chen, Patrick Lambert, Caroline Belser, Cecile Huneau, Stéphane Decroocq, Tetyana Zhebentyayeva, Stéphane Cauet, Weisheng Liu, Joseph Tran, Benjamin Istace, Albert G. Abbott, Aurélien Barré, Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Research Institute of Pomology (RIP CAAS), Chinese Academy of Agricultural Sciences (CAAS), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Génomique métabolique (UMR 8030), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Centre National de Ressources Génomiques Végétales (CNRGV), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire des interactions plantes micro-organismes (LIPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique et Amélioration des Fruits et Légumes (GAFL), CEP Innovation, The Schatz Center for Tree Molecular Genetics,Department of Ecosystem Science and Management, The Pennsylvania State University, Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Ecophysiologie et Génomique Fonctionnelle de la Vigne (UMR EGFV), Université de Bordeaux (UB)-Institut des Sciences de la Vigne et du Vin (ISVV)-Ecole Nationale Supérieure des Sciences Agronomiques de Bordeaux-Aquitaine (Bordeaux Sciences Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Forest Health Research and Education Center,University of Kentucky, (FHC), Ecologie Systématique et Evolution (ESE), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), ANR-11-CHEX-0002,ABRIWG,Génomique comparative et fonctionnelle de la résistance à la sharka et des besoins en froid chez les arbres fruitiers à noyaux(2011), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire des Interactions Plantes Microbes Environnement (LIPME), Pennsylvania State University (Penn State), Penn State System, Liaoning Institute of Pomology, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), University of Kentucky (UK), GET-PACBIO program (« Programme opérationnel FEDER-FSEMIDI-PYRENEES ET GARONNE 2014-2020 »), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Gauthier, Muriel, Organisation et montée en puissance d'une Infrastructure Nationale de Génomique - - France-Génomique2010 - ANR-10-INBS-0009 - INBS - VALID, Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Sciences et Technologies - Bordeaux 1, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and University of Kentucky
Subjects: 0106 biological sciences, 0301 basic medicine, Prunus armeniaca, [SDV]Life Sciences [q-bio], General Physics and Astronomy, adaptation, 01 natural sciences, Gene flow, Population genomics, Plant evolution, [SDV.BV] Life Sciences [q-bio]/Vegetal Biology, Arbre fruitier à noyau, Génétique, Phylogeny, Disease Resistance, Multidisciplinary, biology, Phylogenomics, [SDV] Life Sciences [q-bio], Génomique, Phenotype, [SDV.BV.AP] Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Gene pool, Fruit à noyau, Genome, Plant, Gene Flow, Agricultural genetics, Abricotier, Science, Chromosomes, Plant, Article, General Biochemistry, Genetics and Molecular Biology, Evolution, Molecular, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, domestication, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Selection, Genetic, Domestication, Abricot, Life Cycle Stages, Genetic diversity, [SDV.GEN]Life Sciences [q-bio]/Genetics, Genetic Variation, General Chemistry, Phenotypic trait, biology.organism_classification, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 030104 developmental biology, Evolutionary biology, Fruit, Metagenomics, Adaptation, divergence, 010606 plant biology & botany
Abstract: Among crop fruit trees, the apricot (Prunus armeniaca) provides an excellent model to study divergence and adaptation processes. Here, we obtain nearly 600 Armeniaca apricot genomes and four high-quality assemblies anchored on genetic maps. Chinese and European apricots form two differentiated gene pools with high genetic diversity, resulting from independent domestication events from distinct wild Central Asian populations, and with subsequent gene flow. A relatively low proportion of the genome is affected by selection. Different genomic regions show footprints of selection in European and Chinese cultivated apricots, despite convergent phenotypic traits, with predicted functions in both groups involved in the perennial life cycle, fruit quality and disease resistance. Selection footprints appear more abundant in European apricots, with a hotspot on chromosome 4, while admixture is more pervasive in Chinese cultivated apricots. Our study provides clues to the biology of selected traits and targets for fruit tree research and breeding., The evolutionary and domestication history of apricots is poorly understood. Here, the authors provide four apricot high-quality genome assemblies, the genomes of 578 accessions from natural and cultivated populations, and show that Chinese and European apricots constitute two different gene pools, resulting from independent domestication events.
Published: 2021
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12. TGFβ promotes low IL10-producing ILC2 with profibrotic ability involved in skin fibrosis in systemic sclerosis

Author: Edouard Forcade, Pierre Duffau, Estibaliz Lazaro, Emeline Levionnois, Carlo Chizzolini, Benoit Allard, Patrick Blanco, Julien Izotte, Joël Constans, Pauline Henrot, Pauline Manicki, Damien Leleu, Paôline Laurent, Thomas Pradeu, Valérie Jolivel, Alexis Groppi, Christophe Richez, Thierry Schaeverbeke, Julien Seneschal, Mohamed Jeljeli, Marie-Elise Truchetet, Frédéric Batteux, Cécile Contin-Bordes, Immunology from Concept and Experiments to Translation (ImmunoConcept), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, medicine.medical_treatment, Biopsy, [SDV]Life Sciences [q-bio], [SHS]Humanities and Social Sciences, [SHS.HISPHILSO]Humanities and Social Sciences/History, Philosophy and Sociology of Sciences, Mice, 0302 clinical medicine, Fibrosis, Transforming Growth Factor beta, Immunology and Allergy, Medicine, Lymphocytes, Receptors, Immunologic, Myofibroblasts, Skin, integumentary system, Anti-Inflammatory Agents, Non-Steroidal, Cell Differentiation, Pirfenidone, Middle Aged, 3. Good health, Interleukin-10, Interleukin 10, Cytokine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Collagen, Myofibroblast, medicine.drug, Adult, Pyridones, Immunology, Systemic Sclerosis, General Biochemistry, Genetics and Molecular Biology, Dermal fibroblast, 03 medical and health sciences, Rheumatology, fibroblasts, Animals, Humans, Lectins, C-Type, 030203 arthritis & rheumatology, Scleroderma, Systemic, business.industry, Gene Expression Profiling, medicine.disease, Disease Models, Animal, 030104 developmental biology, inflammation, Cancer research, business, Hepatic fibrosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Transforming growth factor
Abstract: ObjectiveInnate lymphoid cells-2 (ILC2) were shown to be involved in the development of lung or hepatic fibrosis. We sought to explore the functional and phenotypic heterogeneity of ILC2 in skin fibrosis within systemic sclerosis (SSc).MethodsBlood samples and skin biopsies from healthy donor or patients with SSc were analysed by immunostaining techniques. The fibrotic role of sorted ILC2 was studied in vitro on dermal fibroblast and further explored by transcriptomic approach. Finally, the efficacy of a new treatment against fibrosis was assessed with a mouse model of SSc.ResultsWe found that ILC2 numbers were increased in the skin of patients with SSc and correlated with the extent of skin fibrosis. In SSc skin, KLRG1− ILC2 (natural ILC2) were dominating over KLRG1+ ILC2 (inflammatory ILC2). The cytokine transforming growth factor-β (TGFβ), whose activity is increased in SSc, favoured the expansion of KLRG1- ILC2 simultaneously decreasing their production of interleukin 10 (IL10), which regulates negatively collagen production by dermal fibroblasts. TGFβ-stimulated ILC2 also increased myofibroblast differentiation. Thus, human KLRG1- ILC2 had an enhanced profibrotic activity. In a mouse model of SSc, therapeutic intervention-combining pirfenidone with the administration of IL10 was required to reduce the numbers of skin infiltrating ILC2, enhancing their expression of KLRG1 and strongly alleviating skin fibrosis.ConclusionOur results demonstrate a novel role for natural ILC2 and highlight their inter-relationships with TGFβ and IL10 in the development of skin fibrosis, thereby opening up new therapeutic approaches in SSc.
Published: 2021
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13. Finishing bacterial genome assemblies with Mix.

Author: Hayssam Soueidan, Florence Maurier, Alexis Groppi, Pascal Sirand-Pugnet, Florence Tardy, Christine Citti, Virginie Dupuy, and Macha Nikolski
Published: 2013
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14. IPPRED: Server for Proteins Interactions Inference.

Author: Nicolas Goffard, Virginie Garcia, Florian Iragne, Alexis Groppi, and Antoine de Daruvar
Published: 2003
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15. HIV Type-1 Transmission Dynamics in Recent Seroconverters: Relationship with Transmission of drug Resistance and Viral Diversity

Author: Guerric Anies, Alexis Groppi, Rodolphe Thiébaut, François Dabis, Bernard Masquelier, Philippe Morlat, Mathias Bruyand, Hervé Fleury, Didier Neau, Jean-Luc Pellegrin, and Patricia Recordon-Pinson
Subjects: Adult, Male, Human immunodeficiency virus (HIV), HIV Infections, Drug resistance, medicine.disease_cause, Virus, law.invention, Acquired immunodeficiency syndrome (AIDS), law, Drug Resistance, Viral, HIV Seropositivity, medicine, Humans, Pharmacology (medical), Sida, Phylogeny, Pharmacology, Base Sequence, biology, biology.organism_classification, medicine.disease, Virology, HIV Reverse Transcriptase, Infectious Diseases, Transmission (mechanics), Multigene Family, Lentivirus, Immunology, HIV-1, RNA, Viral, Female, Viral disease
Abstract: Background HIV type-1 (HIV-1) has been shown to be frequently transmitted by acutely infected patients. We investigated the relationship between the dynamics of HIV-1 transmission within recently infected patients, the HIV-1 variability and the transmission of antiretroviral drug resistance. Methods We included patients infected between 1996 and 2006, with a plasma sample obtained Results Genotypic resistance was detected in 37/263 (14.1%) patients. Patients were infected by HIV-1 clade B in 222 (84%) cases and with non-B subtypes in 41 (16%). A total of 80 (30.4%) RT sequences were segregated in 24 clusters with bootstrap values >98% for 22 clusters. The frequency of grouping in clusters was higher within B sequences compared with non-B sequences (35.1% versus 4.9%; P-4). Drug-resistant isolates were retrieved in only 3 clusters, but the prevalence of resistance in clustering viruses (10/80, 12.5%) was not different than in isolated sequences. Conclusions The segregation into clusters suggested frequent forward transmission events in patients infected with HIV-1 subtype B, including the possibility of transmission of drug-resistant isolates. These findings warrant increasing prevention efforts and serological screening in the at-risk populations.
Published: 2008
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16. Early Medieval Muslim Graves in France: First Archaeological, Anthropological and Palaeogenomic Evidence

Author: Marie-Hélène Pemonge, Yves Gleize, Marie-France Deguilloux, Fanny Mendisco, Bertrand Houix, Alexis Groppi, Jean-Yves Breuil, Christophe Hubert, Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Archéologie des Sociétés Méditerranéennes (ASM), Université Paul-Valéry - Montpellier 3 (UPVM)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Institut national de recherches archéologiques préventives (Inrap), De la Préhistoire à l'Actuel : Culture, Environnement et Anthropologie (PACEA), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Hubert Curien [Saint Etienne] (LHC), Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), and Institut d'Optique Graduate School (IOGS)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, History, Burial, Archaeological Excavation, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Ethnic group, Social Sciences, lcsh:Medicine, 030105 genetics & heredity, Biochemistry, Geographical Locations, Peninsula, Historical Archaeology, Ethnicity, lcsh:Science, Energy-Producing Organelles, Historical archaeology, palaeogenomic, Multidisciplinary, geography.geographical_feature_category, 05 social sciences, Islam, Genomics, Europe, mitochondria, France, Physical Anthropology, Cellular Structures and Organelles, Period (music), Research Article, Religious Faiths, [SHS.ARCHEO]Humanities and Social Sciences/Archaeology and Prehistory, Bioinformatics, 0507 social and economic geography, Bioenergetics, 050701 cultural studies, 03 medical and health sciences, Politics, Paleoanthropology, Humans, Middle Ages, geography, lcsh:R, Paleontology, Biology and Life Sciences, archaeology, Cell Biology, Archaeology, Anthropology, People and Places, Earth Sciences, Population Groupings, lcsh:Q, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Paleogenetics
Abstract: International audience; The rapid Arab-Islamic conquest during the early Middle Ages led to major political and cultural changes in the Mediterranean world. Although the early medieval Muslim presence in the Iberian Peninsula is now well documented, based in the evaluation of archeological and historical sources, the Muslim expansion in the area north of the Pyrenees has only been documented so far through textual sources or rare archaeological data. Our study provides the first archaeo-anthropological testimony of the Muslim establishment in South of France through the multidisciplinary analysis of three graves excavated at Nimes. First, we argue in favor of burials that followed Islamic rites and then note the presence of a community practicing Muslim traditions in Nimes. Second, the radiometric dates obtained from all three human skeletons (between the 7th and the 9th centuries AD) echo historical sources documenting an early Muslim presence in southern Gaul (i.e., the first half of 8th century AD). Finally, palaeogenomic analyses conducted on the human remains provide arguments in favor of a North African ancestry of the three individuals, at least considering the paternal lineages. Given all of these data, we propose that the skeletons from the Nimes burials belonged to Berbers integrated into the Umayyad army during the Arab expansion in North Africa. Our discovery not only discusses the first anthropological and genetic data concerning the Muslim occupation of the Visigothic territory of Septimania but also highlights the complexity of the relationship between the two communities during this period.
Published: 2016
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17. Composting-Like Conditions Are More Efficient for Enrichment and Diversity of Organisms Containing Cellulase-Encoding Genes than Submerged Cultures

Author: Bernard Henrissat, Françoise Fayolle-Guichard, Senta Heiss-Blanquet, Agnès Hébert, Pedro M. Coutinho, Vincent Lombard, Aurélien Barré, Alexis Groppi, IFP Energies nouvelles (IFPEN), Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Department of Biological Sciences, King Abdulaziz University, Jeddah, Saudi Arabia, ANR-12-BIO-ME-006-01, and Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, [SPI.OTHER]Engineering Sciences [physics]/Other, diversité enzymatique, Hydrolases, bactérie thermophile, Glycobiology, gène codant, Biomass, lcsh:Medicine, biomasse lignocellulosique, 7. Clean energy, Biochemistry, Lignin, Substrate Specificity, facteur enrichissement, Soil, [SPI]Engineering Sciences [physics], Plant Products, Cellulases, Glycoside hydrolase, glycoside hydrolase, Food science, lcsh:Science, Soil Microbiology, Triticum, Fluids, cellulase, Multidisciplinary, biology, Compost, Chemistry, Organic Compounds, Physics, Hydrolysis, Temperature, Straw, food and beverages, Agriculture, Enzymes, biocombustible, Actinobacteria, Populus, Physical Sciences, paroi cellulaire végétale, Research Article, States of Matter, Glycoside Hydrolases, Lignocellulosic biomass, Cellulase, enzyme fongique, engineering.material, Poaceae, complex mixtures, 03 medical and health sciences, Extremophiles, Bacterial Proteins, Biofuel, Polysaccharides, métagénome, [CHIM]Chemical Sciences, compostage, Cellulose, Ecosystem, Bacteria, Thermophile, Ecology and Environmental Sciences, Organic Chemistry, lcsh:R, fungi, Chemical Compounds, Organisms, Biology and Life Sciences, Proteins, Liquids, 15. Life on land, Fungal enzymes, Cellulose binding, biology.organism_classification, Agronomy, 030104 developmental biology, engineering, biology.protein, Enzymology, Metagenome, lcsh:Q, Crop Science
Abstract: International audience; Cost-effective biofuel production from lignocellulosic biomass depends on efficient degradation of the plant cell wall. One of the major obstacles for the development of a cost-efficient process is the lack of resistance of currently used fungal enzymes to harsh conditions such as high temperature. Adapted, thermophilic microbial communities provide a huge reservoir of potentially interesting lignocellulose-degrading enzymes for improvement of the cellulose hydrolysis step. In order to identify such enzymes, a leaf and wood chip compost was enriched on a mixture of thermo-chemically pretreated wheat straw, poplar and Miscanthus under thermophile conditions, but in two different setups. Unexpectedly, metagenome sequencing revealed that incubation of the lignocellulosic substrate with compost as inocu-lum in a suspension culture resulted in an impoverishment of putative cellulase-and hemi-cellulase-encoding genes. However, mimicking composting conditions without liquid phase yielded a high number and diversity of glycoside hydrolase genes and an enrichment of genes encoding cellulose binding domains. These identified genes were most closely related to species from Actinobacteria, which seem to constitute important players of ligno-cellulose degradation under the applied conditions. The study highlights that subtle changes in an enrichment setup can have an important impact on composition and functions of the microcosm. Composting-like conditions were found to be the most successful method for enrichment in species with high biomass degrading capacity.
Published: 2016
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18. Aptamer selection by direct microfluidic recovery and surface plasmon resonance evaluation

Author: Carmelo Di Primo, Eric Dausse, William Palau, Jean-Jacques Toulmé, Aurélien Barré, Chrysanthi Ainali, Gilmar F. Salgado, Ahissan Aimé, Macha Nikolski, Emilie Daguerre, Alain Rico, Alexis Groppi, CBiB, Admin, ARN : régulations naturelle et artificielle, Université Bordeaux Segalen - Bordeaux 2-Institut Européen de Chimie et de Biologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Bioinformatique de Bordeaux, Université Sciences et Technologies - Bordeaux 1, Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Imagerie Moléculaire et Nanobiotechnologies - Institut Européen de Chimie et Biologie (IECB), and Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, X-Box Binding Protein 1, Materials science, Aptamer, Microfluidics, education, Biomedical Engineering, Biophysics, Nanotechnology, 010402 general chemistry, 01 natural sciences, Aptamers, 03 medical and health sciences, RNA Aptamers, Microfluidic recovery, [CHIM] Chemical Sciences, Electrochemistry, RNA Precursors, [CHIM]Chemical Sciences, Surface plasmon resonance, Selection (genetic algorithm), [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Base Sequence, SELEX, SELEX Aptamer Technique, RNA, General Medicine, Aptamers, Nucleotide, Microfluidic Analytical Techniques, Surface Plasmon Resonance, 0104 chemical sciences, Kinetics, 030104 developmental biology, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Systematic evolution of ligands by exponential enrichment, Biotechnology
Abstract: International audience; A surface plasmon resonance (SPR)-based SELEX approach has been used to raise RNA aptamers against a structured RNA, derived from XBP1 pre-mRNA, that folds as two contiguous hairpins. Thanks to the design of the internal microfluidic cartridge of the instrument, the selection was performed during the dissociation phase of the SPR analysis by recovering the aptamer candidates directly from the target immobilized onto the sensor chip surface. The evaluation of the pools was performed by SPR, simultaneously, during the association phase, each time the amplified and transcribed candidates were injected over the immobilized target. SPR coupled with SELEX from the first to the last round allowed identifying RNA aptamers that formed highly stable loop-loop complexes (KD equal to 8 nM) with the hairpin located on the 5’ side of the target. High throughput sequencing of two key rounds confirmed the evolution observed by SPR and also revealed the selection of hairpins displaying a loop not fully complementary to the loop of its target. These candidates were selected mainly because they bound 79 times faster to the target than those having a complementary loop. SELEX coupled with SPR is expected to speed up the selection process because selection and evaluation are performed simultaneously.
Published: 2015

19. Genome-wide association links candidate genes to resistance to Plum Pox Virus in apricot (Prunus armeniaca)

Author: Macha Nikolski, Guillaume Roch, Stéphanie Mariette, Yec’han Laizet, Albert G. Abbott, Patrick Lambert, Fabienne Wong Jun Tai, David Tricon, Aurélien Barré, Aurélie Chague, Jean-Marc Audergon, Stéphane Decroocq, Véronique Decroocq, Alexis Groppi, from patterns to models in computational biodiversity and biotechnology (PLEIADE), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Espèces Fruitières (UREF), Institut National de la Recherche Agronomique (INRA), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Plasticité cérébrale (PC), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Biologie du fruit et pathologie (BFP), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1, Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Laboratoire de Planétologie et Géodynamique UMR6112 (LPG), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Nantes - Faculté des Sciences et des Techniques, Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA), STMicroelectronics [Crolles] (ST-CROLLES), SUEZ ENVIRONNEMENT (FRANCE), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Inria Bordeaux - Sud-Ouest, Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB), Laboratoire de Planétologie et Géodynamique [UMR 6112] (LPG), Université d'Angers (UA)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB), CEP Innovation, Génétique et Amélioration des Fruits et Légumes (GAFL), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, Germplasm, Candidate gene, Physiology, Prunus armeniaca, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, Plant Science, Quantitative trait locus, Genome, Polymorphism, Single Nucleotide, Linkage Disequilibrium, 03 medical and health sciences, Prunus, single nucleotide polymorphism (SNP), apricot, Genotyping, sharka, Disease Resistance, Plant Diseases, 2. Zero hunger, Genetics, biology, Chromosome Mapping, genome-wide association study (GWAS), plum pox virus (PPV) resistance, biology.organism_classification, 030104 developmental biology, Genetics, Population, Plum Pox Virus, Host-Pathogen Interactions, prunus species, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], candidate genes, genome-wide resequencing, Genome, Plant, Reference genome, Genome-Wide Association Study
Abstract: International audience; SummaryIn fruit tree species, many important traits have been characterized genetically by using single-family descent mapping in progenies segregating for the traits. However, most mapped loci have not been sufficiently resolved to the individual genes due to insufficient progeny sizes for high resolution mapping and the previous lack of whole-genome sequence resources of the study species. To address this problem for Plum Pox Virus (PPV) candidate resistance gene identification in Prunus species, we implemented a genome-wide association (GWA) approach in apricot.This study exploited the broad genetic diversity of the apricot (Prunus armeniaca) germplasm containing resistance to PPV, next-generation sequence-based genotyping, and the high-quality peach (Prunus persica) genome reference sequence for single nucleotide polymorphism (SNP) identification.The results of this GWA study validated previously reported PPV resistance quantitative trait loci (QTL) intervals, highlighted other potential resistance loci, and resolved each to a limited set of candidate genes for further study.This work substantiates the association genetics approach for resolution of QTL to candidate genes in apricot and suggests that this approach could simplify identification of other candidate genes for other marked trait intervals in this germplasm.
Published: 2015
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20. The detection of Tel-TrkC chimeric transcripts is more specific than TrkC immunoreactivity for the diagnosis of congenital fibrosarcoma

Author: J. Rivel, Jean P. Leroy, Jean Michel Coindre, Pierre Dubus, Carole Cohen, Anne de Muret, Alexis Groppi, J.-P. Merlio, Hélène Jouan, Jacky Ferrer, and Marie C. Copin
Subjects: Pathology, medicine.medical_specialty, animal structures, Inflammatory myofibroblastic tumour, Infantile myofibromatosis, Nodular fasciitis, Biology, medicine.disease, Pathology and Forensic Medicine, stomatognathic diseases, nervous system, Fusion transcript, hemic and lymphatic diseases, medicine, Immunohistochemistry, Sarcoma, Fibrosarcoma, neoplasms, Adult Fibrosarcoma
Abstract: The t(12;15)(p13;q25) translocation, a recurrent chromosomal abnormality of congenital fibrosarcoma, leads to the expression of a Tel–TrkC fusion transcript. To determine whether detection of the chimeric protein may be helpful for the diagnosis of congenital fibrosarcoma, immunohistochemistry was performed with an anti-TrkC antibody on 26 spindle cell tumours of newborn or young children (n=19) or adults (n=7). Four out of five congenital fibrosarcomas showed TrkC immunoreactivity with cytoplasmic paranuclear staining. However, TrkC immunoreactivity was not restricted to congenital fibrosarcoma and was observed in infantile myofibromatosis, congenital haemangiopericytoma, desmoid tumour, nodular fasciitis, fibrous hamartoma, inflammatory myofibroblastic tumour, and adult fibrosarcoma. RT-PCR analysis was performed on nine cases, including four congenital fibrosarcomas, for which frozen material was available. Tel–TrkC transcripts were detected by RT-PCR in the four congenital fibrosarcomas analysed, but not in the five other spindle cell tumours. Furthermore, several Tel–TrkC transcripts encoding for kinase isoforms of the Tel–TrkC protein were detected in congenital fibrosarcoma and may be involved in oncogenesis. The reciprocal TrkC–Tel transcript was detected in only one congenital fibrosarcoma. While the detection of a Tel–TrkC fusion transcript is a recurrent feature of congenital fibrosarcoma, TrkC immunoreactivity does not appear specific for the diagnosis of fibromatous paediatric tumours. Copyright © 2000 John Wiley & Sons, Ltd.
Published: 2001
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21. Expression of Trk Isoforms in Brain Regions and in the Striatum of Patients with Alzheimer's Disease

Author: Alexis Groppi, Etienne C. Hirsch, Yves Agid, Jean-Philippe Merlio, T. Anne Vital, Baptiste Faucheux, Pierre Dubus, Claude Vital, and Florence Boissière
Subjects: Adult, Male, medicine.medical_specialty, Striatum, Developmental Neuroscience, Alzheimer Disease, Internal medicine, medicine, Animals, Humans, Protein Isoforms, Receptor, trkB, Rats, Wistar, Receptor, trkA, Cholinergic neuron, Aged, Aged, 80 and over, biology, Putamen, Ventral striatum, Brain, Neurodegenerative Diseases, Parkinson Disease, Human brain, Middle Aged, Choline acetyltransferase, Corpus Striatum, Rats, Endocrinology, medicine.anatomical_structure, nervous system, Neurology, Trk receptor, biology.protein, Female, Neurotrophin
Abstract: The TrkAII tyrosine kinase receptor differs from the TrkAI isoform by an insertion of six amino acids in the extracellular domain. We used RT-PCR to determine their respective distribution in rat and human brain. Only trkAII transcripts were detected in 12 rat brain regions, while both trkAI and trkAII transcripts were detected in the cerebellum and pituitary gland. In human, both trkAI and trkAII transcripts were detected in the frontal, temporal, and occipital cortex and thalamus, while only trkAI transcripts were detected in the hippocampus and cerebellum. In the caudate and putamen, trkAII transcripts were exclusively detected. Thereafter, we studied the expression of TrkA isoforms in the striatum of five patients with Alzheimer's disease (AD), four patients with non-AD dementia, seven patients with Parkinson's disease, and six paired nondemented elderly control individuals. In controls and non-AD patients, a constant expression of trkAII transcripts was detected within all striatum parts. In AD patients, a heterogeneous decrease in trkAII expression was observed in the caudate, putamen, and ventral striatum, resulting either in a drop of trkAII transcript levels or in a weak coamplification of trkAII and trkAI transcripts. The alteration of TrkAII gene expression paralleled those of choline acetyltransferase. Together with previous data, this suggests that the alteration of trk gene expression could contribute to a decrease in NGF binding sites and its protective effects on cholinergic neurons of AD patients.
Published: 2000
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22. Regulation of Gene Expression During the Vegetative Incompatibility Reaction in Podospora anserina: Characterization of Three Induced Genes

Author: Christian Barreau, Joël Bégueret, Nathalie Bourges, Corinne Clavé, and Alexis Groppi
Subjects: Signal peptide, Genes, Fungal, Molecular Sequence Data, Protein Sorting Signals, Biology, Podospora anserina, Open Reading Frames, Ascomycota, Bacterial Proteins, Gene Expression Regulation, Fungal, Gene expression, Genetics, Amino Acid Sequence, RNA, Messenger, Cloning, Molecular, Gene, Gene Library, Plant Proteins, Regulation of gene expression, Messenger RNA, cDNA library, RNA, Fungal, Translation (biology), Sequence Analysis, DNA, biology.organism_classification, Research Article
Abstract: Vegetative incompatibility in fungi limits the formation of viable heterokaryons. It results from the coexpression of incompatible genes in the heterokaryotic cells and leads to a cell death reaction. In Podospora anserina, a modification of gene expression takes place during this reaction, including a strong decrease of total RNA synthesis and the appearance of a new set of proteins. Using in vitro translation of mRNA and separation of protein products by two-dimensional gel electrophoresis, we have shown that the mRNA content of cells is qualitatively modified during the progress of the incompatibility reaction. Thus, gene expression during vegetative incompatibility is regulated, at least in part, by variation of the mRNA content of specific genes. A subtractive cDNA library enriched in sequences preferentially expressed during incompatibility was constructed. This library was used to identify genomic loci corresponding to genes whose mRNA is induced during incompatibility. Three such genes were characterized and named idi genes for genes induced during incompatibility. Their expression profiles suggest that they may be involved in different steps of the incompatibility reaction. The putative IDI proteins encoded by these genes are small proteins with signal peptides. IDI-2 protein is a cysteine-rich protein. IDI-2 and IDI-3 proteins display some similarity in a tryptophan-rich region.
Published: 1998
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23. Statistical Evaluation of Diagnostic and Prognostic Features of CD30+ Cutaneous Lymphoproliferative Disorders

Author: A. De Mascarel, Karen Pulford, Christine Bodemer, M. F. Avril, Alexis Groppi, Michèle Delaunay, D. Y. Mason, Jean-Philippe Merlio, Marie Beylot-Barry, Claire Beylot, A de Muret, Pascal Joly, Sophie Dalac, Martine Bagot, P. Michel, Jacques Bosq, Janine Wechsler, and Béatrice Vergier
Subjects: Male, Pathology, medicine.medical_specialty, Oncogene Proteins, Fusion, CD30, Ki-1 Antigen, Lymphoproliferative disorders, CD15, Disease, Skin Diseases, Pathology and Forensic Medicine, law.invention, Diagnosis, Differential, Antigen, immune system diseases, law, hemic and lymphatic diseases, Biomarkers, Tumor, medicine, Humans, Polymerase chain reaction, integumentary system, Diagnostic Tests, Routine, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Mucin-1, DNA, Neoplasm, Middle Aged, Protein-Tyrosine Kinases, Prognosis, medicine.disease, Survival Analysis, Lymphoproliferative Disorders, Lymphoma, T-Cell, Cutaneous, Lymphoma, Evaluation Studies as Topic, Cancer research, Immunohistochemistry, Female, Surgery, France, Lymphoma, Large B-Cell, Diffuse, Tumor Suppressor Protein p53, Anatomy, business
Abstract: Several clinical and histopathologic features of 65 CD30+ cutaneous lymphoproliferations were evaluated for their diagnostic value between CD30+ primary versus secondary cutaneous lymphomas and for their prognostic significance. Primary cutaneous disease, spontaneous regression, and absence of extracutaneous spreading (but not age < or =60 years) were associated with a better prognosis. Epithelial membrane antigen, BNH9, CD15 or CBF.78 antigen were expressed in all types of cutaneous lymphoproliferations. However, epithelial membrane antigen immunoreactivity was more frequently expressed in CD30+ secondary cutaneous large-cell lymphoma. Among CD30+ primary cutaneous large-cell lymphoma, CD15 expression was only seen in localized skin lesions. P53 expression was not associated with spontaneous regression, extracutaneous spreading, or survival. Nested reverse transcriptase-polymerase chain reaction allowed the detection of NPM-ALK transcripts in 10 of 26 CD30+ primary and in 3 of 11 secondary cutaneous large-cell lymphomas. The ALK protein was detected in only 1 of 50 primary and in 4 of 15 secondary cutaneous CD30+ lymphoproliferations. In CD30+ primary cutaneous lymphoproliferation, NPM-ALK transcripts might be expressed by very rare normal or tumoral cells that are undetectable by immunohistochemistry. However, the expression of either NPM-ALK transcripts or ALK-protein was not correlated with prognosis or age in CD30+ cutaneous lymphoproliferations.
Published: 1998
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24. Expression of NGF receptors in normal and pathological human thymus

Author: E. Labouyrie, Dominique Carles, Jean-François Velly, Antoine de Mascarel, Pierre Dubus, Alexis Groppi, Marie Parrens, and Jean-Philippe Merlio
Subjects: Adult, Male, Pathology, medicine.medical_specialty, animal structures, Stromal cell, Adolescent, Thymoma, Immunology, Cell, Receptors, Nerve Growth Factor, Thymus Gland, Biology, Receptor, Nerve Growth Factor, Fetus, Western blot, Reference Values, Proto-Oncogene Proteins, medicine, Humans, Immunology and Allergy, Low-affinity nerve growth factor receptor, Tissue Distribution, Nerve Growth Factors, RNA, Messenger, Receptor, trkA, Child, Receptor, Aged, medicine.diagnostic_test, Carcinoma, Infant, Receptor Protein-Tyrosine Kinases, Thymus Neoplasms, Middle Aged, medicine.disease, medicine.anatomical_structure, Nerve growth factor, nervous system, Neurology, Trk receptor, Cancer research, Female, Thymus Hyperplasia, Neurology (clinical), Thymus hyperplasia
Abstract: The expression of NGF receptors was investigated in normal human thymus and in thymic hyperplasias, thymomas and thymic carcinomas. By RT-PCR, we detected TrkAI transcripts encoding for the high-affinity NGF receptor. Western blot analysis showed the presence of both TrkA and p75 NGFR proteins. In normal thymuses, epithelial subcapsular and medullar cells were TrkA immunoreactive. Interdigitated medullar cells were stained for both TrkA and p75 NGFR . While epithelial cells of normal thymuses or benign thymomas exhibited a TrkA positive–p75 NGFR negative phenotype, a switch to a TrkA negative–p75 NGFR positive phenotype was observed in malignant epithelial cell tumours and was associated with cell proliferation-associated MIB1 expression. Our results argue for a local role of NGF and its receptors on thymic stromal cells both in normal and neoplastic conditions.
Published: 1998
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25. Utilisation d'une Grille de Calcul (GRISBI) pour le Traitement de Données NGS (New Generation Sequencing)

Author: Florence Maurier, Alexis Groppi, Aurélien Barré, Delphine Naquin, Aurélien Roult, Clément Gauthey, Christophe Blanchet, Tiphaine Martin, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Modèles et algorithmes pour la Bioinformatique et la Visualisation d'informations, (MABIOVIS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), and Sciencesconf.org, CCSD
Subjects: Grille de calcul, Assemblage de novo, NGS, [INFO.INFO-DC] Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], [INFO.INFO-DC]Computer Science [cs]/Distributed, Parallel, and Cluster Computing [cs.DC], Gestionnaire de workflow, Calcul intensif
Abstract: International audience; Utilisation d'une Grille de Calcul (GRISBI) pour le Traitement de Données NGS (New Generation Sequencing)
Published: 2011

26. Genome evolution in yeasts

Author: Valérie Barbe, Laurence Cattolico, Isabelle Lesur, Alix Kerrest, Hélène Ferry-Dumazet, Fabrice Confanioleri, Serge Casaregola, Emmanuel Talla, Véronique Anthouard, Jean-Marie Beckerich, Laurence Ma, Odile Ozier-Kalogeropoulos, Nicolas Jauniaux, Nicolas Goffard, Jacky de Montigny, David James Sherman, Antoine de Daruvar, Serge Potier, Guy-Franck Richard, Romain Koszul, Pascal Durrens, Anna Babour, Sophie Oztas, Emmanuelle Beyne, Christian Marck, Patrick Wincker, Emmanuelle Fabre, Stefan Pellenz, Bernard Dujon, Florence Hantraye, Eric Westhof, Cécile Fairhead, Micheline Wésolowski-Louvel, Cécile Neuvéglise, Gilles Fischer, Laurence Despons, Christophe Hennequin, Jean Weissenbach, Marie-Laure Straub, Audrey Suleau, Stéphanie Barnay, Jean-Marc Nicaud, Macha Nikolski, Claude Gaillardin, Claudine Bleykasten, Jean-Luc Souciet, Fredj Tekaia, Philippe Joyet, Rym Kachouri, Sylvie Blanchin, Bénédicte Wirth, Héloïse Muller, Christiane Bouchier, Maria Zeniou-Meyer, Ingrid Lafontaine, Jeanne Boyer, Monique Bolotin-Fukuhara, Ivan Zivanovic, Claude Scarpelli, Bernard Caudron, Agnès Thierry, Dominique Swennen, Alexis Groppi, Anita Boisramé, Michel Aigle, Lionel Frangeul, Marc Lemaire, Génétique Moléculaire des Levures, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Collection de Levures d'Intérêt Biotechnologique et Laboratoire de Génétique Moléculaire et Cellulaire, Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Dynamique, évolution et expression de génomes de microorganismes (DEEGM), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Génomique (Plate-Forme) - Genomics Platform, Institut Pasteur [Paris] (IP), Génomique métabolique (UMR 8030), Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Génétique des Interactions Macromoléculaires, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Unité de Microbiologie et génétique (UMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Architecture et réactivité de l'ARN (ARN), Logiciels et Banques de Données, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Génomique (Plate-Forme), Institut Pasteur [Paris], Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)
Subjects: MESH: Tandem Re, MESH: Research Support, Non-U.S. Gov't, Genome, MESH: Saccharomyces cerevisiae Proteins, RNA, Transfer, Gene Duplication, Yeasts, Conserved Sequence, MESH: Evolution, Molecular, Segmental duplication, Genomic organization, Genetics, SACCHAROMYCES CEREVISIAE, 0303 health sciences, Multidisciplinary, MESH: Conserved Sequence, MESH: Yeasts, MESH: Gene Duplication, MESH: Synteny, Genome project, MESH: Chromosomes, Fungal, Tandem Repeat Sequences, MESH: Genome, Fungal, Chromosomes, Fungal, Genome, Fungal, GENETIC MAPPING, Genome evolution, Saccharomyces cerevisiae Proteins, Genes, Fungal, Molecular Sequence Data, Biology, Synteny, Evolution, Molecular, 03 medical and health sciences, GENOME ORGANIZATION, Molecular evolution, YEAST, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Gene, 030304 developmental biology, Comparative genomics, STRUCTURE DU GENOME, MESH: Molecular Sequence Data, 030306 microbiology, MESH: RNA, Transfer, MOLECULAR EVOLUTION, MESH: Tandem Repeat Sequences, Evolutionary biology, RNA, Ribosomal, MESH: RNA, Ribosomal, MESH: Genes, Fungal
Abstract: Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.
Published: 2004
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27. New strategy for the representation and the integration of biomolecular knowledge at a cellular scale

Author: Isabelle Dutour, Aurélien Barré, Roland Barriot, Nicolas Goffard, Alexis Groppi, David James Sherman, Jerome Poix, Antoine de Daruvar, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Centre de Bioinformatique de Bordeaux (CBIB), CGFB, and Sherman, David James
Subjects: data-mining, computer.internet_protocol, gene enrichment, [INFO.INFO-OH]Computer Science [cs]/Other [cs.OH], Saccharomyces cerevisiae, Biology, Bioinformatics, computer.software_genre, Set (abstract data type), 03 medical and health sciences, Similarity (psychology), Databases, Genetic, Genetics, Relevance (information retrieval), Representation (mathematics), 030304 developmental biology, Structure (mathematical logic), 0303 health sciences, Gene Expression Profiling, 030302 biochemistry & molecular biology, Probabilistic logic, Computational Biology, Articles, Genomics, Expression (mathematics), [INFO.INFO-OH] Computer Science [cs]/Other [cs.OH], Systems Integration, classification, Data mining, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], computer, Sequence Analysis, XML, Software
Abstract: International audience; The combination of sequencing and post-sequencing experimental approaches produces huge collections of data that are highly heterogeneous both in structure and in semantics. We propose a new strategy for the integration of such data. This strategy uses structured sets of sequences as a unified representation of biological information and defines a probabilistic measure of similarity between the sets. Sets can be composed of sequences that are known to have a biological relationship (e.g. proteins involved in a complex or a pathway) or that share similar values for a particular attribute (e.g. expression profile). We have developed a software, BlastSets, which implements this strategy. It exploits a database where the sets derived from diverse biological information can be deposited using a standard XML format. For a given query set, BlastSets returns target sets found in the database whose similarity to the query is statistically significant. The tool allowed us to automatically identify verified relationships between correlated expression profiles and biological pathways using publicly available data for Saccharomyces cerevisiae. It was also used to retrieve the members of a complex (ribosome) based on the mining of expression profiles. These first results validate the relevance of the strategy and demonstrate the promising potential of BlastSets.
Published: 2004
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28. Differential expression of NGF receptors in human thymic epithelial tumors

Author: Jean-François Velly, Alexis Groppi, E. Labouyrie, Marie Parrens, Antoine de Mascarel, Pierre Dubus, and Jean-Philippe Merlio
Subjects: medicine.medical_specialty, animal structures, Thymoma, Receptors, Nerve Growth Factor, Thymus Gland, Biology, Pathology and Forensic Medicine, Stroma, Reticular cell, Internal medicine, medicine, Humans, Protein Isoforms, Receptor, trkA, Receptor, Hyperplasia, Reverse Transcriptase Polymerase Chain Reaction, Carcinoma, Nuclear Proteins, Antigens, Nuclear, Cell Biology, Thymus Neoplasms, Phenotype, Immunohistochemistry, Epithelium, Endocrinology, Nerve growth factor, medicine.anatomical_structure, nervous system, Trk receptor, Cancer research
Abstract: NGF receptor (TrkA and p75NGFR) expression was investigated in human thymuses, including normal thymuses, thymic hyperplasias, thymomas and thymic carcinomas. TrkAI but not TrkAII transcripts were demonstrated by RT-PCR. In normal thymuses, immunohistochemistry revealed a restricted TrkA-immunoreactivity to epithelial and interdigitated reticular cells, while only interdigitaded reticular cells were immunoreactive for p75NGFR. Thymocytes were negative for both receptors. A switch from the normal TrkA positive-p75NGFR negative phenotype to a TrkA negative-p75NGFR positive phenotype was found in histologically aggressive epithelial cell tumors, suggesting that NGF and its receptors are potentially involved in thymus stroma organogenesis and proliferation.
Published: 1999

29. Expression of Neurotrophins and their Receptors in Human Bone Marrow

Author: Jacky Ferrer, E. Labouyrie, Antoine de Mascarel, Jean-Philippe Merlio, Marie Parrens, Josy Reiffers, Pierre Dubus, Alexis Groppi, and François Xavier Mahon
Subjects: Adult, Pathology, medicine.medical_specialty, Stromal cell, animal structures, Molecular Sequence Data, Bone Marrow Cells, Gestational Age, Tropomyosin receptor kinase B, Receptors, Nerve Growth Factor, Tropomyosin receptor kinase A, Biology, Tropomyosin receptor kinase C, Pathology and Forensic Medicine, Immunoenzyme Techniques, Fetus, medicine, Low-affinity nerve growth factor receptor, Animals, Humans, Protein Isoforms, Cell Lineage, Amino Acid Sequence, Nerve Growth Factors, Receptor, DNA Primers, Base Sequence, Reverse Transcriptase Polymerase Chain Reaction, Receptor Protein-Tyrosine Kinases, Molecular biology, Rats, nervous system, Trk receptor, embryonic structures, biology.protein, RNA, Female, Stromal Cells, Neurotrophin, Regular Articles
Abstract: The expression of neurotrophins and their receptors, the low-affinity nerve growth factor receptor (p75 LNGFR ) and the Trk receptors (TrkA, TrkB, and TrkC), was investigated in human bone marrow from 16 weeks fetal age to adulthood. Using reverse transcription-polymerase chain reaction, all transcripts encoding for catalytic and truncated human TrkB or TrkC receptors were detected together with trk AI transcripts, whereas trk AII transcripts were found only in control nerve tissues. Transcripts for the homologue of the rat truncated TrkC(ic113) receptor were identified for the first time in human tissue. Stromal adventitial reticular cells were found immunoreactive for all neutrophin receptors. In contrast, hematopoietic cell types were not immunoreactive for p75 LNGFR but showed immunoreactivity for one or several Trk receptors. TrkA immunoreactivity was found in immature erythroblasts. Catalytic TrkB immunoreactivity was observed in eosinophilic metamyelocytes and polymorphonuclear cells. Truncated TrkB immunoreactivity was found in erythroblasts and megacaryocytes. Immunoreactivity for both catalytic and truncated TrkC receptor was observed in promyelocytes, myelocytes, some polymorphonuclear cells and megacaryocytes. Neutrophin transcript levels appeared higher at fetal than at adult stages, no variation in Trk family transcript levels was observed. The local expression of neurotrophin genes suggests a wide range of paracrine and/or autocrine mode of action through their corresponding receptors within the bone marrow.
Published: 1999

30. Glutathione S-transferase class ? in French alcoholic cirrhotic patients

Author: Alexis Groppi, A. Iron, Joël Bégueret, Christiane Coutelle, Patrice Couzigou, and Benoît Fleury
Subjects: Adult, Liver Cirrhosis, medicine.medical_specialty, Alcoholic liver disease, Cirrhosis, Genotype, Deoxyribonucleotides, Molecular Sequence Data, Polymerase Chain Reaction, Gastroenterology, law.invention, chemistry.chemical_compound, law, Internal medicine, Genetics, medicine, Humans, Metabolic disease, Genetics (clinical), Polymerase chain reaction, Glutathione Transferase, Ethanol, Base Sequence, biology, Glutathione, Middle Aged, medicine.disease, Alcoholism, Blotting, Southern, Glutathione S-transferase, chemistry, Biochemistry, biology.protein
Abstract: The lack of glutathione S-transferase mu (GST mu) was examined in 45 healthy French Caucasians and 45 alcoholic cirrhotic French Caucasians: microsamples of blood were taken and DNA amplified by the polymerase chain reaction. We have concluded that there is no relationship between this genotype and the development of alcoholic cirrhosis in these heavy consumers of ethanol.
Published: 1991
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31. Improved methods for genotype determination of human alcohol dehydrogenase (ADH) at ADH 2 and ADH 3 loci by using polymerase chain reaction-directed mutagenesis

Author: A Iron, Joël Bégueret, and Alexis Groppi
Subjects: Genotype, Clinical Biochemistry, Molecular Sequence Data, Biology, Polymerase Chain Reaction, law.invention, law, Humans, Site-directed mutagenesis, Gene, Polymerase chain reaction, Alleles, Alcohol dehydrogenase, Genetics, chemistry.chemical_classification, Binding Sites, Base Sequence, urogenital system, Biochemistry (medical), Alcohol Dehydrogenase, Molecular biology, Isoenzymes, Enzyme, Directed mutagenesis, chemistry, Mutagenesis, biology.protein, Restriction fragment length polymorphism, hormones, hormone substitutes, and hormone antagonists
Abstract: The human gene for producing alcohol dehydrogenase (ADH; EC 1.1.1.1) is polymorphic at ADH 2 and ADH 3 loci. Until now, the study of this polymorphism required liver biopsy or allele-specific radioactive probes. We have used directed mutagenesis by the polymerase chain reaction (PCR) to amplify and analyze the genotype of ADH 2 and ADH 3 loci. Thus, we could determine easily and unambiguously the complete genotype at these two loci by using a microsample of blood and restriction fragment length polymorphism after DNA amplification by PCR.
Published: 1990

32. Role of Alcohol Dehydrogenase Polymorphism in Ethanol Metabolism and Alcohol-Related Diseases

Author: Joël Bégueret, Benoît Fleury, Christiane Coutelle, A. Iron, Alexis Groppi, Patrice Couzigou, and A. Cassaigne
Subjects: medicine.medical_specialty, Alcoholic liver disease, Ethanol, Aldehyde dehydrogenase, Alcohol, Biology, medicine.disease, Isozyme, chemistry.chemical_compound, Endocrinology, chemistry, Internal medicine, medicine, biology.protein, Genetic variability, Ethanol metabolism, Alcohol dehydrogenase
Abstract: In alcohol toxicity, a lot of data point to genetic factors associated with environmental factors. These genetic factors can intervene at different levels : genetic variability in the distribution of polymorphic alcohol and aldehyde dehydrogenase isozymes (Bosron, et al., 1988) could play a role in determining individual difference in ethanol metabolism and toxicity. In the future, other polymorphisms in alcohol metabolism may be described. Polymorphism is also to be considered in detoxication and/or target organ metabolism (as collagen polymorphism in alcoholic cirrhosis)(Weiner, et al., 1988).
Published: 1990
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33. Valeur diagnostique et pronostique de critères cliniques et biologiques dans une série de lymphoproliférations cutanées CD30+

Author: Jean-Philippe Merlio, Claire Beylot, Janine Wechsler, Karen Pulford, Martine Bagot, B. Vergier, Alexis Groppi, P. Michel, Michèle Delaunay, Jacques Bosq, A. De Mascarel, Marie Beylot-Barry, A. De Muret, M. F. Avril, Pascal Joly, Sophie Dalac, D. Y. Mason, and Christine Bodemer
Subjects: Gastroenterology, Internal Medicine
Published: 1998
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34. Small RNA-Seq reveals novel miRNAs shaping the transcriptomic identity of rat brain structures

Author: Alexis Groppi, Mélissa Valere, Anaïs Soula, Alexandre Favereaux, María José López-González, Vicky Ury-Thiery, Macha Nikolski, Marc Landry, Nikolski, Macha, Centre de Bioinformatique de Bordeaux (CBIB), CGFB, Physiopathologie des Reseaux Neuronaux Medullaires, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Laboratoire Angiogenèse et Micro-environnement des Cancers (LAMC), and Université Sciences et Technologies - Bordeaux 1-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Resource, 0301 basic medicine, Small RNA, Health, Toxicology and Mutagenesis, Central nervous system, Hippocampus, Plant Science, Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Transcriptome, 03 medical and health sciences, 0302 clinical medicine, microRNA, medicine, ComputingMilieux_MISCELLANEOUS, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], Ecology, Neurogenesis, Resources, Olfactory bulb, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Synaptic plasticity, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], 030217 neurology & neurosurgery
Abstract: Small RNA-Seq of the rat central nervous system reveals known and novel miRNAs specifically regulated in brain structures and correlated with the expression of their predicted target genes, suggesting a critical role in the transcriptomic identity of brain structures., In the central nervous system (CNS), miRNAs are involved in key functions, such as neurogenesis and synaptic plasticity. Moreover, they are essential to define specific transcriptomes in tissues and cells. However, few studies were performed to determine the miRNome of the different structures of the rat CNS, although a major model in neuroscience. Here, we determined by small RNA-Seq, the miRNome of the olfactory bulb, the hippocampus, the cortex, the striatum, and the spinal cord and showed the expression of 365 known miRNAs and 90 novel miRNAs. Differential expression analysis showed that several miRNAs were specifically enriched/depleted in these CNS structures. Transcriptome analysis by mRNA-Seq and correlation based on miRNA target predictions suggest that the specifically enriched/depleted miRNAs have a strong impact on the transcriptomic identity of the CNS structures. Altogether, these results suggest the critical role played by these enriched/depleted miRNAs, in particular the novel miRNAs, in the functional identities of CNS structures.

35. Genome Sequence of Mycoplasma meleagridis Type Strain 17529

Author: Alain Blanchard, Elhem Yacoub, Pascal Sirand-Pugnet, Boutheina Ben Abdelmoumen Mardassi, Laboratoire de Microbiologie Moléculaire, Vaccinologie et Développement Biotechnologique (LR11IPT01), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Biologie du fruit et pathologie (BFP), Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA), This work received financial support from the Tunisian National Ministry of Higher Education and Scientific Research., We thank Christophe Hubert from the Genome-Transcriptome facility of Bordeaux and Alexis Groppi and Aurélien Barré from the Bordeaux Bioinformatics Center for genome sequencing, assembly, and integration into the MolliGen database., and Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2
Subjects: Strain atcc, Genetics, Whole genome sequencing, Strain (biology), Mycoplasma meleagridis, Biology, biology.organism_classification, Pathogenicity, Genome, 3. Good health, Type (biology), [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Prokaryotes, Molecular Biology, Pathogen
Abstract: Mycoplasma meleagridis is a prominent turkey bacterial pathogen associated with airsacculitis and reproductive disorders. Notwithstanding the economic losses caused by M. meleagridis , its genome has still not been sequenced. For a better understanding of its genetic background and pathogenicity mechanisms, we sequenced the genome of M. meleagridis type strain ATCC 25294.
Published: 2015
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36. Learning Automata on Protein Sequences

Author: François Coste, Goulven Kerbellec, Biological systems and models, bioinformatics and sequences (SYMBIOSE), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique, Institut National de Recherche en Informatique et en Automatique (Inria), Alain Denise and Pascal Durrens and Stéphane Robin and Eduardo Rocha and Antoine de Daruvar and Alexis Groppi, Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Inria Rennes – Bretagne Atlantique
Subjects: [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Proteins, Pattern Discovery, ACM: J.: Computer Applications/J.3: LIFE AND MEDICAL SCIENCES/J.3.0: Biology and genetics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Grammatical Inference, Automata
Abstract: National audience; Pattern discovery is limited to position-specific characterizations like Prosite's patterns or profile-HMMs which are unable to handle, for instance, dependencies between amino acids distant in the sequence of a protein, but close in its three-dimensional structure. To overcome these limitations, we propose to learn automata on proteins. Inspired by grammatical inference and multiple alignment techniques, we introduce a sequence-driven approach based on the idea of merging ordered partial local multiple alignments (PLMA) under preservation or consistency constraints and on an identification of informative positions with respect to physico-chemical properties . The quality of the characterization is asserted experimentally on two difficult sets of proteins by a comparison with (semi)-manually designed patterns of Prosite and with state-of-the-art pattern discovery algorithms. Further leave-one-out experimentations show that learning more precise automata allows to gain in accuracy by increasing the classification margins.
Published: 2006

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